Neutrophils direct preexisting matrix to initiate repair in damaged tissues

Internal organs heal injuries with new connective tissue, but the cellular and molecular events of this process remain obscure. By tagging extracellular matrix around the mesothelium lining in mouse peritoneum, liver and cecum, here we show that preexisting matrix was transferred across organs into wounds in various injury models. Using proteomics, genetic lineage-tracing and selective injury in juxtaposed organs, we found that the tissue of origin for the transferred matrix likely dictated the scarring or regeneration of the healing tissue. Single-cell RNA sequencing and genetic and chemical screens indicated that the preexisting matrix was transferred by neutrophils dependent on the HSF-integrin AM/B2-kindlin3 cascade. Pharmacologic inhibition of this axis prevented matrix transfer and the formation of peritoneal adhesions. Matrix transfer was thus an early event of wound repair and provides a therapeutic window to dampen scaring across a range of conditions. Rinkevich and colleagues show that preexisting matrix is transferred by neutrophils across organs into injured sites in a manner dependent on integrin activation.

Automated summary

Research shows that damaged organs can repair wounds by transferring preexisting matrix through neutrophils. The source of the transferred matrix may determine the scarring or regeneration of the healing tissue. Blocking this transfer process through pharmacological inhibition can prevent matrix transfer and the formation of peritoneal adhesions.